Preliminary studies have demonstrated that rats treated with lead (200 mg/kg/day) during development (days 2-30) were significantly more polydipsic after lithium adminstration than were nonlead-treated, paired controls. Animals were tested 30 or more days after cessation of lead administration. This finding has been duplicated in nearly two dozen paired litters of lead treated and control Long-Evans rats during a one year period, and has been found to persist until the animals were at least six months of age. The animals tested showed no other consistent behavioral, biochemical or pathological alteration. This research proposal will attempt to localize and define the physiological alterations in lithium-induced drinking caused by the infantile lead administration. The involvement of the peripheral renin-angiotensin system, known to be elevated by lithium, will be investigated in lead and control animals using radioimmunoassay. Other known dipsogenic agents will be administered by various routes to determine if infantile lead exposure causes increased polydipsia to other agents, either alone or after lithium pretreatment. Since central dopaminergic neurons are known to be essential to lithium-induced polydipsia, lead-treated and control rats will be depleted of catecholamines in the central nervous system using 6-hydroxydopamine. The alterations in drinking responses to lithium and other dipsogenic agents will be measured after generalized and specific catecholamine depletions. The completion of these studies should offer a foundation for studying other mechanisms which are affected by the lead administration as well as the alterations in other physiologically related systems. Most importantly, these studies provide a model for the study of lead toxicity on the central nervous system of developing rats that is not only extremely reproducible, but also easily quantifiable since it utilizes an easily determined function, water consumption.